191471-52-0

191471-52-0 structure

Name: LY 379268
Chemical Name: (1R,4R,5S,6R)-4-amino-2-oxabicyclo[3.1.0]hexane-4,6-dicarboxylic acid
CAS Number: 191471-52-0
Molecular Formula: C₇H₉NO₅
Molecular Weight: 187.15
Catalog: Signaling Pathways GPCR/G Protein mGluR
Create Date: 2017-10-29 06:52:23
Modify Date: 2024-02-18 16:34:17
LY379268 is a potent, selective and brain-penetrant mGlu2/3R agonist with EC50 values of 2.69 nM (mGlu2) and 4.48 nM (mGlu3). LY379268 has no activity on human mGlu 1a, 4a, 5a or 7a receptors. LY379268 has antioxidant and neuroprotective effects[1][2].

Name	(1R,4R,5S,6R)-4-amino-2-oxabicyclo[3.1.0]hexane-4,6-dicarboxylic acid

Description	LY379268 is a potent, selective and brain-penetrant mGlu2/3R agonist with EC50 values of 2.69 nM (mGlu2) and 4.48 nM (mGlu3). LY379268 has no activity on human mGlu 1a, 4a, 5a or 7a receptors. LY379268 has antioxidant and neuroprotective effects[1][2].
Related Catalog	Signaling Pathways >> GPCR/G Protein >> mGluR Research Areas >> Neurological Disease
Target	hmGluR2:2.69 nM (EC50) hmGluR3:4.48 nM (EC50) hmGluR2:14.1 nM (Ki) hmGluR3:5.8 nM (Ki)
In Vitro	Treatment of 9-weeks (9w) astrocytes with LY379268 (0.1 μM; 24-48 hours) results in an increase in mGlu3R and Nrf2 protein levels and SOD activity, and decreases mitochondrial ROS levels and apoptosis. mGlu3R activation in aged astrocytes also preventS hippocampal neuronal death induced by Aβ1-42 in co-culture assays. Activation of mGlu3R in aged astrocytes haS an anti-oxidant effect and protected hippocampal neurons against Aβ-induced neurotoxicity[3].
In Vivo	For LY379268, when a 3 mg/kg dose is given prior to an intraplantar injection of carrageenan, the inflammatory hyperalgesia that developed is significantly delayed, without affecting the inflammation of the paw[2]. In a model of mouse tail withdrawal to warm water, LY379268 (12 mg/kg; i.p.), given before a subcutaneous tail injection of capsaicin, reduces the subsequent neurogenic hyperalgesia[2].LY354740 prevents release of glutamate in the striatum in freely moving rats and to attenuate morphine withdrawal-associated activation of locus coeruleus neurones, thought to be caused by an increased release of glutamate[2].
References	[1]. J A Monn, et al. Synthesis, pharmacological characterization, and molecular modeling of heterobicyclic amino acids related to (+)-2-aminobicyclo[3.1.0] hexane-2,6-dicarboxylic acid (LY354740): identification of two new potent, selective, and systemically active agonists for group II metabotropic glutamate receptors. J Med Chem. 1999 Mar 25;42(6):1027-40. [2]. E F Sharpe, et al. Systemic pre-treatment with a group II mGlu agonist, LY379268, reduces hyperalgesia in vivo. Br J Pharmacol. 2002 Mar;135(5):1255-62. [3]. Juan Turati, et al. Antioxidant and neuroprotective effects of mGlu3 receptor activation on astrocytes aged in vitro. Neurochem Int. 2020 Nov;140:104837.

Molecular Formula	C₇H₉NO₅
Molecular Weight	187.15
Exact Mass	187.04800
PSA	109.85000

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